Cathepsin B Inhibitors for Targeted Cancer Therapy

Abstract

Cathepsin B is a ubiquitous and tightly controlled cysteine protease having been implicated in a wide variety of cellular processes such as protein conversion, activation, and signaling. Cathepsin B has also been found to have many roles in several stages of tumor progression up to and beyond metastasis. As a result, current research has focused on either identifying potential cathepsin B inhibitors that can directly be used for treatment or as a model for drug development. Development of cathepsin B inhibitors is still in progress with none currently reaching clinical trials. Some drugs such as VBY-825 and the quinolone antibiotic nitroxoline have shown promise in direct application, while others such as chalcones, curcumin, and IGFBP-4 can be used as models for developing future cathepsin B inhibitors for clinical use. Drugs already successful in clinical trials to treat other conditions unrelated to cathepsin B, such as osteoporosis with odanacatib, have similar analogues that have been shown to inhibit cathepsin B and not only could be used as a model for new cathepsin B inhibitor development, but also result in reaching the market sooner due to a known high safety profile. Further studies beyond developing cathepsin B inhibitors should focus on a combinatory treatment of cathepsin B inhibitor with chemotherapy, radiation, and/ or inhibition of other proteins involved with tumor progression. This combinatory approach has been shown to be highly effective in tumor cell sensitization and death.